Lysosomal storage diseases/disorders describe several dozen rare genetic metabolic disorders. Lysosomal storage disorders are caused by lysosomal dysfunction usually as a consequence of deficiency of an enzyme used in the metabolism of lipids, glycoproteins or glycosaminoglycans (formerly known as mucopolysaccharides). Lysosomes break down unwanted matter via enzymes. Lysosomal disorders occur when a particular enzyme is compromised or missing. As a result, the undesired substances accumulate in the cell.
Lysosomal storage diseases can cause severe symptoms and/or can severely shorten a patient's lifespan. There are no cures for lysosomal storage diseases and treatment is mostly symptomatic, although enzyme replacement therapy (ERT) have been tried with some success. However, at least some enzymes utilized for ERT cannot pass the blood-brain barrier, thereby limiting their effect on neurological symptoms, which can be quite severe in some lysosomal storage diseases.
For example, mucopolysaccharidoses (MPS) are diseases in which one or more steps in the metabolic pathway for the degradation of glycosaminoglycans (GAGS) are compromised, and the body is unable to properly break down the glycosaminoglycans. The compromised ability of the body to produce α-Glucosamide N-acetyltransferase results in MPS IIIC, also known as Sanfilippo syndrome type C. The clinical symptoms of Sanfilippo syndrome include behavioral problems, intellectual disability, coarse facial features and walking difficulties, and generally, people afflicted with the syndrome have lifespans extending only into their teenage years. Currently, there is no known treatment that satisfactorily addresses the above symptoms, particular the neurological ones. Although the affected enzyme may be produced and given to the patient as ERT, the ERT enzyme does not cross the blood-brain barrier, and therefore cannot reach the brain to treat the cause of the neurological symptoms.
Pharmacological chaperones can help to stabilize the defective enzymes produced by patients that have lysosomal storage disorders. However, chaperones are often specific to certain lysosomal storage disorders, and many diseases still have no known medicines. There is thus a need for new therapeutic compounds that can be used to prevent and/or treat various lysosomal storage disorders such as MPSIIIC that provide patients with a higher quality of life and achieve a better clinical outcome.